Kin Fon Leong

Mutation study for 9 genes in 23 unrelated patients with autosomal recessive congenital ichthyosis in Japan and Malaysia

Autosomal recessive congenital ichthyosis (ARCI) is heterogeneous group of ichthyosis and consists of Harlequin ichthyosis (HI, MIM #242500), lamellar ichthyosis (LI, MIM #242304) and congenital ichthyosiform erythroderma (CIE, MIM #242100). Harlequin ichthyosis shows the severest phenotype and used to be almost fatal at birth [1]. Even milder types of ARCI severely influence quality of life of patients. To date, mutations in 9 causative genes have been reported in ARCI, including ATPbinding cassette, subfamily a, member 12 (ABCA12) [2,3], transglutaminase 1 (TGM1) [2,3], arachidonate lipoxygenase 3 [2,3], arachidonate 12-lipoxygenase, 12R type (ALOX12B) [2,3], NIPA-like domain containing 4 [2,3], cytochrome P450, family 4, subfamily F, polypeptide 22 [2,3], lipase, family member N [2,3], patatin-like phospholipase domain-containing 1 [3] and ceramide synthase 3 [4]. However, mutations in these genes have been found in about 78% of ARCI patients [2]. In this study, we performed genetic analyses in 23 unrelated patients with ARCI. Sixteen out of 23 patients were from Japan, and 7 patients from Malaysia. Clinically and histopathologically, 3 patients were diagnosed as HI, 2 patients as LI, and 18 patients as CIE. All experiments in this study were approved by Medical Ethical Committee of Kurume University School of Medicine, and conducted according to Declaration of Helsinki Principles. Written informed consent was obtained from each individual. Mutation and polymorphism analyses of 9 causative genes were performed, basically according to the methods described previously [5]. Briefly, genomic DNA was extracted from peripheral blood and PCR-direct sequencing was performed for all exons and their flanking intron boundaries in all 9 genes. Primer sequences for all 9 genes are shown in Supplemental data (Table S1). Primers which we designed using online Primer3 plus tool are indicated by red-colored letters (Table S1) [6]. We detected mutations in 17 (74%) of 23 patients. Mutations on both alleles were detected in 14 of 17 patients, while only one mutation could be detected in 3 patients. Ten (44%) of 17 patients showed mutations in ABCA12, 6 (26%) patients in TGM1, and one (4%) patient in ALOX12B (Fig. 1A). Eleven unreported mutations in ARCI were identified in this study and 4 out of 11 were missense mutations, 2 were in ABCA12 and

Cupping Therapy May be Harmful for Eczema: A PubMed Search

Eczema is a common childhood atopic condition and treatment is with emollients, topical corticosteroids, and avoidance of possible triggers. S. aureus colonization is a common complication. As there is no immediate cure, many parents seek alternative therapies that claim unproven therapeutic efficacy. We report a girl with long history of treatment noncompliance. After practicing a long period of dietary avoidance and supplementation, the grandparents took her to an alternative medicine practitioner. Following cupping therapy and acupuncture, the child developed blistering and oozing over her back the next day, which rapidly evolved to two large irregular-edge deep ulcers. She was treated with intravenous antibiotics and received multidisciplinary supportive intervention. Using search words of  “cupping,” “eczema,” and “atopic dermatitis,” only two reports were found on PubMed. Therapeutic efficacy was claimed but not scientifically documented in these reports. Childhood eczema is an eminently treatable atopic disease. Extreme alternative therapy seems not to be efficacious and may even be associated with serious undesirable sequelae. Physicians should be aware of various alternative treatment modalities and be prepared to offer evidence-based advice to the patients with eczema and their families.

Staphylococcal-scalded skin syndrome: evaluation, diagnosis, and management

BackgroundStaphylococcal-scalded skin syndrome (SSSS), also known as Ritter disease, is a potentially life-threatening disorder and a pediatric emergency. Early diagnosis and treatment is imperative to reduce the morbidity and mortality of this condition. The purpose of this article is to familiarize physicians with the evaluation, diagnosis, and treatment of SSSS.Data sourcesA PubMed search was completed in Clinical Queries using the key terms “Staphylococcal scalded skin syndrome” and “Ritter disease”.ResultsSSSS is caused by toxigenic strains of Staphylococcus aureus. Hydrolysis of the amino-terminal extracellular domain of desmoglein 1 by staphylococcal exfoliative toxins results in disruption of keratinocytes adhesion and cleavage within the stratum granulosum which leads to bulla formation. The diagnosis is mainly clinical, based on the findings of tender erythroderma, bullae, and desquamation with a scalded appearance especially in friction zones, periorificial scabs/crusting, positive Nikolsky sign, and absence of mucosal involvement. Prompt empiric treatment with intravenous anti-staphylococcal antibiotic such as nafcillin, oxacillin, or flucloxacillin is essential until cultures are available to guide therapy. Clarithromycin or cefuroxime may be used should the patient have penicillin allergy. If the patient is not improving, critically ill, or in communities where the prevalence of methicillin-resistant S. aureus is high, vancomycin should be used.ConclusionA high index of suspicion is essential for an accurate diagnosis to be made and treatment promptly initiated.

Measles: a disease often forgotten but not gone

Measles (rubeola) is a highly contagious vaccine-preventable disease caused by the measles virus-a virus of the Paramyxoviridae family. The illness typically begins with fever, runny nose, cough, and pathognomonic enanthem (Koplik spots) followed by a characteristic erythematous, maculopapular rash. The rash classically begins on the face and becomes more confluent as it spreads cephalocaudally. Laboratory confirmation of measles virus infection can be based on a positive serological test for measles-specific immunoglobulin M antibody, a four-fold or greater increase in measles-specific immunoglobulin G between acute and convalescent sera, isolation of measles virus in culture, or detection of measles virus ribonucleic acid by reverse transcriptase-polymerase chain reaction. Complications occur in 10% to 40% of patients, and treatment is mainly symptomatic. Bacterial superinfections, if present, should be properly treated with antibiotics. To eradicate measles, universal childhood immunisation and vaccination of all susceptible individuals with measles vaccine would be ideal. In developed countries, routine immunisation with measles-containing vaccine is recommended, with the first and second doses at ages 12 to 15 months and 4 to 6 years, respectively. The World Health Organization recommends that the first and second doses of measles-containing vaccine be given at ages 9 months and 15 to 18 months, respectively, in countries with high rates of measles transmission.

An 8-Year-Old Child with Delayed Diagnosis of Netherton Syndrome

We report an 8-year-old boy with Netherton syndrome who was misdiagnosed and treated as severe atopic dermatitis. The diagnosis of Netherton syndrome was not made until the child was 8 years of age. We discuss the pitfalls in the diagnosis and alert physicians to the proper and early diagnosis of this syndrome. The child was treated with a low dose (0.25 mg/kg) of oral acitretin and a topical moisturizer with marked improvement of his skin and pruritus in 2 months. At 6-month follow-up, the skin was almost clear of erythema and scaling, and the hair was longer and stronger. The dose of acitretin was reduced to 0.12 mg/kg for another 6 months and then discontinued.

A Case of Congenital Syphilis Presenting with Unusual Skin Eruptions

Once believed to be a rare disease in developed countries, recent data suggest that there is a surge in incidence of congenital syphilis in many developed countries. Diagnosis of congenital syphilis can be difficult because more than two-thirds of affected infants are asymptomatic at birth, and signs of symptomatic infants may be nonspecific or subtle. On top of this, some affected infants may have atypical presentations. Familiarity with the diverse presentations is essential to diagnosis. We report a 2-week-old male infant with congenital syphilis whose cutaneous manifestations included diffuse, erythematous keratoderma with desquamation and fissures on his hands and feet, multiple linear scaly fissures at the angles of his mouth, and onychauxis of the fingernails and toenails To our knowledge, diffuse, erythematous keratoderma of the hands and feet and thick nails have not been reported previously in congenital syphilis.